New Interim Data About Combination Oral Contraceptives

WAYNE, N.J., March 25, 2011 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals Inc. today announced that interim results from a large, prospective, observational cohort safety study offer insights into the increased risk of venous thromboembolism (VTE), or blood clots, which is a well-established risk in women who use combination oral contraceptives (COCs), also known as "the Pill".

Specifically, the new data provides healthcare providers with information regarding when the VTE risk associated with COCs is highest.  The risk of VTE is highest during the first year of COC use and the new data suggest that this increased risk is greatest during the first six months.  This risk is greatest when first starting the Pill and when restarting the same or a different Pill after a four week or greater break.  

The new data are from the ongoing, Long-Term Active Surveillance Study for Oral Contraceptives (LASS) – a large, multinational, prospective cohort, five-year follow-up safety study to the European Active Surveillance (EURAS) study. Cardiovascular events, including VTE, were the main clinical outcomes studied in LASS.   Together, these two studies will provide data for up to ten years on women using various COCs.  

"As a leader in women's contraception, we believe it is important for Bayer to take the lead in studying and communicating the risks and benefits of COCs," said Leo Plouffe, MD, Vice President, US Medical Affairs, Women's Healthcare, Bayer HealthCare Pharmaceuticals.  "The new information is helpful because while healthcare providers have long known about the risk of VTE associated with COCs, there was little information to indicate that there was an increased risk in women restarting COCs after a four week or greater period of non-use.  This new information should provide both healthcare providers and women who choose a COC for contraception with additional information when making the decision to implement a pause in their COC routine."  

Following the submission of the interim analysis, Bayer worked with the US Food and Drug Administration (FDA) and updated the Prescribing Information for YAZ® (3 mg drospirenone / 0.02 mg ethinyl estradiol) in the US.  Bayer will continue to work with the FDA to update the Prescribing Information for all of its oral contraceptives in the US.

Like pregnancy, the use of COCs is associated with an increased risk of blood clots, which can be life-threatening. However, pregnancy increases the risk of blood clots as much or more than the use of COCs. These events are uncommon in healthy women using COCs.

Since 2001, Bayer commissioned independent investigators to conduct large-scale observational studies assessing the risk of VTE in women using COCs containing a variety of progestins, including drospirenone.  The results from these studies have been shared with the FDA and other regulatory authorities.

"Increased VTE risk is associated with any COC, and Bayer is committed to studying the safety and efficacy of our products.   Birth control pills are among the most systematically studied medicines available today," said Dr. Plouffe.

Several studies have investigated the relative risks of thromboembolism in women using drospirenone-containing COCs compared to women using COCs containing other progestins.

Bayer's post-marketing studies have shown that the risk of VTE in a COC formulation containing 3 mg drospirenone in combination with 0.03 mg ethinyl estradiol is comparable to that of any COCs in those studies.(1,2)

Two other published studies – one case-control study and one retrospective cohort study – have suggested that the risk of VTE occurring in drospirenone/ethinyl estradiol users was between the risk associated with levonorgestrel-containing COCs and desogestrel/gestodene-containing COCs.(3,4)  In April 2010, the FDA approved an update to the YAZ Prescribing Information regarding these two studies and indicated that they may be unreliable, specifically:

• With regard to the case-control study, the Prescribing Information indicates that, "…the number of [3 mg drospirenone/0.03 mg ethinyl estradiol] cases was very small (1.2% of all cases) making the risk estimates unreliable."  
• Concerning the retrospective cohort study, the Prescribing Information indicates that, "The relative risk for [3 mg drospirenone/0.03 mg ethinyl estradiol] users in the retrospective cohort study was greater than that for users of other COCs when considering women who used the products for less than one year.  However, these one-year estimates may not be reliable because the analysis may include women of varying risk levels.  Among women who used the product for one to four years, the relative risk was similar for users of [3 mg drospirenone/0.03 mg ethinyl estradiol] to that for users of other COC products."

Women should not use YAZ if they smoke and are over age 35.  Smoking increases the risk of serious side effects from the Pill, which can be life-threatening, including blood clots, stroke or heart attack.  This risk increases with age and number of cigarettes smoked.

YAZ increases the risk of serious conditions including blood clots, stroke, and heart attack. The risk of blood clots is highest during the first year of use.  

In addition, YAZ contains drospirenone, a different kind of hormone that for some may increase potassium too much. Therefore, women should not take YAZ if they have kidney, liver, or adrenal disease because this could cause serious heart and health problems.  Women who are on daily, long-term treatment for a chronic condition with medications that may also increase potassium (see below), should consult with their healthcare provider as they should have a blood test to check their potassium level during the first month of taking YAZ.

Important Safety Information

What is YAZ® prescribed for?

For women who choose the Pill for birth control, YAZ is approved to:

• Prevent pregnancy -  99% effective when taken as directed
• Treat premenstrual dysphoric disorder (PMDD)
  • YAZ is not approved to treat Premenstrual Syndrome (PMS), a less serious set of symptoms occurring before your period
• Treat moderate acne in women at least 14 years of age

Who should not take YAZ?

Women should not use YAZ if they smoke and are over age 35. Smoking increases the risk of serious side effects from the Pill, which can be life-threatening, including blood clots, stroke or heart attack. This risk increases with age and number of cigarettes smoked.

Women should not use YAZ if they have kidney, liver, or adrenal disease because this could cause serious heart and health problems, or if they have or have had blood clots, certain cancers, history of heart attack or stroke, or if they are or may be pregnant.

What are the most serious risks of taking YAZ?

YAZ increases the risk of serious conditions including blood clots, stroke, and heart attack. The risk of blood clots is highest during the first year of use.  This risk is greatest when first starting the Pill and when restarting the same or a different Pill after a 4 week or greater break.

In addition, YAZ contains drospirenone, a different kind of hormone that for some may increase potassium too much. Women should consult their healthcare provider if they are on daily long-term treatment for a chronic condition with medications that may also increase potassium (see below), as they should have a blood test to check their potassium level during the first month of taking YAZ.

What medications may increase potassium?

NSAIDs—ibuprofen (Motrin®, Advil®), naproxen (Aleve® and others) when taken long-term and daily for arthritis or other problems, potassium-sparing diuretics (spironolactone and others), potassium supplementation, ACE inhibitors (Capoten®, Vasotec®, Zestril®, and others), angiotensin-II receptor antagonists (Cozaar®, Diovan®, Avapro®, and others), aldosterone antagonists, and heparin.

What are the most common side effects?

In the contraception and moderate acne clinical trials, the most common side effects were headache/migraine, menstrual irregularities, nausea/vomiting, breast pain/tenderness, and mood changes.

In the PMDD clinical trials, the most common side effects were menstrual irregularities, nausea, headache, breast tenderness, fatigue, irritability, decreased libido, weight gain, and mood changes.

YAZ does not protect against HIV infection (AIDS) or other STDs.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information about YAZ, including boxed warning, available at http://yaz-us.com/.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions.  As a specialty pharmaceutical company, Bayer HealthCare Pharmaceuticals provides products for Diagnostic Imaging, General Medicine, Hematology, Neurology, Oncology and Women's Healthcare.  The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

BAYER®, the Bayer Cross®, YAZ®, and Aleve® are trademarks of Bayer.  All other trademarks are the property of their respective owners.

Forward-Looking Statements

This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

(1)  Dinger J et al. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance study on Oral Contraceptives based on 142,475 women-years of observation. Contraception. 2007;75:344–354.

(2) Seeger J et al. Risk of Thromboembolism in Women Taking Ethinylestradiol/Drospirenone and Other Oral Contraceptives. Obstetrics & Gynecology. 2007;110:587–593.

(3)  Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ. 2009;339:b2921.

(4)  Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890.

SOURCE Bayer HealthCare Pharmaceuticals Inc.